Inhibitory effects of sodium valproate on oxidative phosphorylation.
Sodium valproate (VP) inhibited oxidative phosphorylation in isolated rat liver mitochondria. State 3 rates of oxygen consumption with glutamate as substrate were 80% of control values at a low VP concentration (24 microM). At 240 microM, there was more than 50% inhibition of glutamate and alpha-ketoglutarate state 3 rates. Succinate state 3 rates were 80% of control values, and uncoupling was noted at 2400 microM VP. These VP effects were similar to those of propionate and isovalerate, suggesting a common mechanism of toxicity. Inhibition of mitochondrial oxidative phosphorylation may explain why VP intoxication causes a hepatocerebral disorder that resembles Reye syndrome.
D000818:Animals; D005971:Glutamates / Q000378:metabolism; D066298:In Vitro Techniques; D007656:Ketoglutaric Acids / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013386:Succinates / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology*
D005971:Glutamates; D007656:Ketoglutaric Acids; D013386:Succinates; D014635:Valproic Acid